CD4 Count Research Articles

Prevalence of virological failure and associated factors among adult individuals on highly active antiretroviral treatment (HAART) in public health facilities at Tulu Bolo Town, Southwest Shoa, Ethiopia, 2024

IntroductionThe goal of antiretroviral therapy for HIV infection is to achieve and maintain virological suppression. Review of charts of adult HIV-positive patients at public health facilities in Tulu Bolo Town reveals that approximately 6.07% of patients did not respond to first-line antiretroviral medication. The identified gap indicates that the study area’s virological failure prevalence and contributing factors are not well-documented. Thus, this study’s objectives are to evaluate prevalence and close a knowledge gap about factors associated with virological failure.ObjectiveThe objective of this study was to assess the prevalence of virological failure and associated factors among patients taking highly active antiretroviral therapy in Tulu Bolo Town Health facilities, Oromia, Ethiopia, 2024.MethodsHealth facility-based cross-sectional study was conducted at Tulu Bolo Town in public health facilities from 30 September 2024 to 30 October 2024. The total sample sizes of 274 records of clients were selected using simple random sampling technique. Data were cleaned and entered into EPI info version 7.2.0.1 and exported to SPSS version 20.0 for further analysis. The association was identified using binary logistic regression model. An adjusted odds ratio with 95% confidence intervals (CI) was computed to identify the presence and strength of association. Finally, statistically significant variables were declared at a p-value of < 0.05 along with 95% CI.ResultsA total of 274 charts of HIV-positive clients were included in the study. The magnitude of virological failure was 12.8% (95%CI 9, 17%). Baseline CD4 count < 200 (AOR 6.1, 95%CI 2.06, 18.43), clients infected with TB (AOR 4.8 95%CI 1.78, 12.96), treatment interruption (AOR 3.05, 95% CI 1.06, 8.77), and adherence (AOR 3.67, 95%CI 1.39, 9.66) were statistically significant association.Conclusion and recommendationThe overall prevalence of virological failure of this study was high as compared to standard. Baseline CD4 count, TB infection, treatment interruption, and adherence were significant factors. Health facility ART provider and HIV/AIDS program manager should give special attention for clients with history of TB co-infection and CD4 count < 200 needs care and support and providing TB preventive therapy.

High propensity for multidrug-resistant pneumococcal shedding among adults living with HIV on stable antiretroviral therapy in Malawi

Abstract Background People living with HIV (PLHIV) on antiretroviral therapy (ART) are still at risk of pneumococcal disease and have over two-fold higher pneumococcal carriage prevalence than HIV-uninfected adults (HIV- adults). Carriage is a risk factor for pneumococcal disease, antimicrobial resistance (AMR) emergence, and transmission. Therefore, we tested whether the high prevalence of pneumococcal carriage in PLHIV on ART is associated with increased bacterial density, shedding and AMR. Methods We recruited asymptomatic PLHIV on ART for more than one year (PLHIV-ART>1yr) and HIV- adults. Nasopharyngeal swabs were collected on days 3, 7, 14, 21, and 28, followed by monthly collections for 12 months, while shedding samples were collected on days 3, 21, and 28. Peripheral blood was collected on day 3 to measure CD4 count and HIV viral load. Pneumococcal carriage density and shedding were assessed using standard bacterial culture, and multiple carriage was detected through whole plate sweep sequencing. AMR profiling was conducted using disk diffusion and E-test. Findings PLHIV-ART>1yr had a higher propensity for high-density carriage (adjusted Odds Ratio 1.67, 95% CI 1.07-2.60, p=0.023). Moreover, PLHIV-ART>1yr are more likely to shed pneumococci than HIV- adults (aOR 2.52, 95% CI 1.06-6.00, p=0.037), with carriage density identified as an important risk factor for shedding (aOR 3.35, 95% CI 1.55-7.24, p=0.002). Aerosol shed isolates from PLHIV-ART>1yr were mostly multidrug-resistant (62% 18/29, 95% CI 48%-77%). Interpretation These findings indicate that PLHIV-ART>1yr remain at high risk of pneumococcal disease and could also be an important reservoir for shedding multidrug-resistant pneumococci.

Effectiveness of a national reflex laboratory cryptococcal antigen screening programme for people with advanced HIV disease in South Africa: a nationwide-sampled cohort study (CAST-NET)

Background: Cryptococcal antigen (CrAg) screening and pre-emptive treatment of antigenaemia can reduce mortality among people living with HIV. Setting: We evaluated the effectiveness of a national CrAg screening program in South Africa. Methods: We enrolled a retrospective cohort of adults aged ≥18 years with a CD4 count <100 cells/µL and antigenaemia at 442 facilities in a stratified-random sample of 27 sub-districts, 2017-2019. We determined a composite outcome of incident cryptococcal meningitis or death through 6-months. Results: Overall, 99% (85,791/86,274) of eligible patients had CrAg testing in the study sub-districts; 5,124 (6.0%) tested CrAg-positive. Among 1,651 with imaged medical records and without concurrent meningitis, 76% (1,261/1,651) were outpatients. CrAg results were documented in records for 75% (1,245/1,651). Only 39% (649/1,651) had a meningitis symptom review documented at a median of 14 days (IQR, 5-44) from their CrAg blood draw. Fluconazole was dispensed for 50% (827/1,651) but only 32% (523/1,651) had an adequate daily dose of ≥800 mg dispensed. The proportion with meningitis or death within 6-months was 23% (382/1,651; 95%CI, 19%-27%). Hospitalised patients had a 2.29 higher adjusted odds of meningitis/death within 6-months versus outpatients (95% CI, 1.72-3.04; p<0.001). Conclusion: Nationwide reflex laboratory CrAg screening was successfully implemented. However, challenges existed for healthcare providers to act on positive CrAg results to exclude meningitis and dispense pre-emptive antifungal therapy. Our findings emphasise the critical need for improved linkage from reflex CrAg screening to clinical care, in both ambulatory and in-patient settings, to maintain the effectiveness of this intervention.

Record linkage without patient identifiers: Proof of concept using data from South Africa’s national HIV program

Linkage between health databases typically requires patient identifiers such as names and personal identification numbers. We developed and validated a record linkage strategy to combine administrative health databases without identifiers for South Africa’s public sector HIV program. We linked CD4 counts and HIV viral loads from South Africa’s TIER.Net with the National Health Laboratory Service (NHLS) database for patients receiving care between 2015–2019 in Ekurhuleni District (Gauteng Province). Linkage variables were result value, specimen collection date, facility of collection, year and month of birth, and sex. We used three matching strategies: exact matching on exact values of all variables, caliper matching allowing a ± 5 day window on result date, and specimen barcode matching using unique specimen identifiers. A sequential linkage approach applied specimen barcode, followed by exact, and then caliper matching. Exact and caliper matching were validated using barcodes (available for 34% of records in TIER.Net) as a “gold standard”. Performance measures were sensitivity, positive predictive value (PPV), share of patients linked, and percent increase in data points. We attempted to link 2,017,290 laboratory test results from TIER.Net (523,558 unique patients) with 2,414,059 NHLS test results. Exact matching achieved 69.0% sensitivity and 95.1% PPV. Caliper matching achieved 75% sensitivity and 94.5% PPV. Sequential linkage matched 41.9% using specimen barcodes, 51.3% through exact matching, and 6.8% through caliper matching, for 71.9% (95% CI: 71.9, 72.0) of test results matched overall, with 96.8% (95% CI: 96.7, 97.1) PPV and 85.9% (95% CI: 85.7, 85.9) sensitivity. This linked 86.0% (95% CI: 85.9, 86.1) of TIER.Net patients to the NHLS (N = 1,450,087), increasing laboratory results in TIER.Net by 62.6%. Linkage of TIER.Net and NHLS without patient identifiers attained high accuracy and yield without compromising privacy. The integrated cohort provides a more complete laboratory test history and supports more accurate HIV program indicator estimates.

Unmasking Advanced HIV Infection: A Case of Refractory Thrombocytopenia Misdiagnosed as Immune Thrombocytopenic Purpura

Thrombocytopenia is a frequent hematological abnormality in individuals with Human Immunodeficiency Virus (HIV) infection and can be the initial presenting sign. Its clinical picture can closely mimic primary Immune Thrombocytopenic Purpura (ITP), leading to diagnostic delays and inappropriate management. This report highlights a case where an HIV diagnosis was revealed during the workup for refractory thrombocytopenia. A 39-year-old female presented with fatigue and gingival bleeding. She had a previous diagnosis of ITP and had been treated intermittently, but the thrombocytopenia repeatedly recurred. Physical examination was notable for oral candidiasis. Laboratory investigations confirmed severe thrombocytopenia with a platelet count of 4,000/µL. Subsequent serological testing was reactive for HIV, with a CD4 count of 136 cells/µL. The patient was managed for severe thrombocytopenia and opportunistic infection, with a plan to initiate antiretroviral therapy. In conclusion, this case underscores the critical importance of including HIV infection in the differential diagnosis for patients presenting with new-onset or refractory thrombocytopenia. Clinical clues, such as opportunistic infections, should prompt immediate HIV screening to ensure timely diagnosis and initiation of definitive therapy, thereby preventing misdiagnosis and improving patient outcomes.

Rapid Initiation of Antiretroviral Therapy Suppresses T Cell Pathological Proliferation and Improves Immune Recovery in People Living with HIV

PurposeInitiating antiretroviral therapy promptly (rapid ART) is linked to better immune recovery in people with HIV (PWH), although its specific effects on immune dysregulation remain partially understood. We have discovered a “pathological proliferation” phenomenon, marked by T cell over-proliferation and exhaustion in PWH, potentially hindering full immune recovery. The objective of this research is to examine how rapid ART affects T-cell pathological proliferation, immune recovery, and systemic inflammation in PWH.Patients and MethodsIn this cross-sectional study (conducted at Beijing Youan Hospital, Capital Medical University, China, from April 1 to September 18, 2022), we recruited 39 PWH, including 23 in the rapid ART group (within 30 days) and 16 in the non-rapid ART group (after 180 days). Fasting venous blood samples were collected in the morning. Immune phenotypes of T cells were analyzed using mass cytometry and Luminex.ResultsThe rapid ART group demonstrated a significant decline in Ki67⁺ CD4⁺ and CD8⁺ T cells. Within this group, a higher percentage of naive T (TN) cells was observed in CD4⁺ T cells, along with a remarkable reduction in Ki67 expression. Additionally, CD8⁺ T cells in the rapid ART group exhibited an increased presence of TN cells while showing a decreased proportion of PD-1/HLA-DR/CD38 high-expressing cells. In addition, the rapid ART group exhibited significantly lower IL-18 levels. TN cells (CD31+ HLA-DR− CD38− CD57− PD-1−) and central memory T (TCM) cells (HLA-DR+ CD38− PD-1− CD57−) that were not suppressed by rapid ART showed significant correlations with baseline CD4 counts, HIV loads, and recent CD4/CD8 ratio.ConclusionThese findings suggest rapid ART may curb pathological T cell proliferation and improved immune recovery in PWH. Despite these benefits, persistent immune activation in some individuals highlights the need for targeted immune monitoring and potential adjunctive interventions to optimize long-term immune health in PWH.

Effects of antiretroviral resistance on outcomes and health care resource utilisation among people with HIV in the United States and Europe: a real-world survey

Background: Despite advances in antiretroviral therapy (ART), resistance remains a barrier to effective HIV treatment. Objective: This study evaluated associations between ART drug resistance and treatment adherence, health care resource utilisation (HCRU), and quality of life (QoL) among people with HIV. Methods: A retrospective, observational study was conducted using the Adelphi HIV Disease Specific Programme™ (DSP) between 2021 and 2023 across the United States and Europe. Data were collected via physician surveys, patient record forms, and patient self-completion forms. Results: Data for 2006 people with HIV and resistance testing were contributed by 290 physicians, and 586 people with HIV provided patient data. Overall, 286 people with HIV (14%) had documented resistance. People with HIV with resistance had received more ART regimens than those without resistance (p < 0.0001) and had lower viral suppression rates (p = 0.004) and lower CD4 counts (p = 0.032). People with HIV with resistance reported lower treatment adherence (p = 0.017) but similar QoL compared to those without resistance. People with HIV with resistance also had significantly more HIV-related hospitalisations than those without resistance (p = 0.022). Conclusions: ART resistance was associated with higher HCRU and poorer health outcomes in people with HIV, underscoring the need for continued focus on adherence and resistance management.

Comparative analysis of glucuronoxylomannogalactan (GXMGal) and glucuronoxylomannan (GXM) antibody responses and their associations with cryptococcal disease status in people living with HIV.

Cryptococcosis remains a major cause of mortality in people with HIV (PWH). While glucuronoxylomannan-binding immunoglobulin G (GXM-IgG) levels have been associated with disease status and survival, the clinical significance of glucuronoxylomannogalactan-binding IgG (GXMGal-IgG) has not been investigated. We analyzed serological data from two previously reported cohorts of PWH: a prospective asymptomatic South African cohort (67 cryptococcal antigen [CrAg]-positive, 130 CrAg-negative), and a Vietnamese case-control cohort (30 with symptomatic cryptococcal meningitis [CM], 30 without), both followed for mortality for six months. Serum/plasma GXMGal-IgG levels were quantified by enzyme-linked immunosorbent assay and compared to previously reported GXM-IgG levels. Logistic regression adjusted for age, sex, and CD4 count examined associations between antibody levels and CrAg positivity or CM status, while Cox proportional hazards models adjusted for CD4 count estimated associations with time to mortality. Higher GXMGal-IgG was associated with CrAg positivity (odds ratio [OR], 1.64; 95% CI, 1.14-2.36), not CM status. Among individuals with asymptomatic cryptococcal antigenemia, higher GXMGal-IgG trended toward higher survival (hazards ratio [HR], 0.67; 95% CI, 0.41-1.09), but this was not statistically significant and no significant survival benefit was observed for those with CM. GXMGal-IgG was associated with CrAg positivity and showed a modest trend toward survival for individuals with asymptomatic cryptococcal antigenemia but had limited predictive value for CM or mortality. These findings in antigenemia largely parallel previous observations for GXM-IgG, although associations observed were generally weaker. Further studies are needed to clarify the immune response to GXMGal and its potential diagnostic or prognostic significance.

Understanding Predictors of Lifelong Initiation and Follow-up Treatment for adolescents and youth living with HIV (UPLIFT): an integrated prospective cohort in Eastern Cape, South Africa.

Adolescents living with HIV (ALHIV) are a priority population for achieving global HIV prevention and treatment targets but experience poorer outcomes than adults. Long-term follow-up is essential to understand their transition into adulthood. By linking self-reported survey data with routine laboratory records, we established a social science clinical cohort of ALHIV South Africa's Eastern Cape to explore factors shaping their long-term health and well-being. Eligible participants were adolescents who were part of a three-wave quantitative cohort of ALHIV and not living with HIV (2014-2018) and had consented (adolescent and caregiver) to having their self-reported interviews linked with routine health records (n=1563). Adolescents were recruited into the existing three-wave cohort through clinic and community-based methods (97% enrolment, >90% retention over three waves). Between 2019 and 2022, we abstracted laboratory test records from the National Health Laboratory Services database for all eligible participants, with matching based on demographic variables. Individuals with at least one HIV-related record form our 'lifelong social science cohort', a total of 956 ALHIV (852 of 1107 ALHIV and 104 of 456 HIV-uninfected). A total of 32 886 laboratory test records from 2004 to 2023 were matched through three rounds of data extraction, using iteratively refined record-linking searches. Most records were viral load (8864) and CD4 count (6801) results, with a median of 10 (IQR: 7-14) and 8 (IQR: 5-11) tests per matched adolescent, respectively. Overall, 956 of 1563 adolescents (61%) were successfully linked to laboratory data, including 852 of 1107 (77%) ALHIV. Analysis of the matched cohort survey-laboratory data provided several insights. Self-reported antiretroviral therapy adherence was strongly associated with viral suppression, even after adjusting for covariates. The strongest predictors of suppression were not reporting missed doses in the past 3 days, past week and not missing clinic appointments in the past year. Among adolescent girls and young women living with HIV, access to safe and affordable facilities, and kind and respectful staff were associated with a higher likelihood of multiple improved HIV-related outcomes, including viral suppression. Exposure to sexual and intimate partner violence predicted worse viral load outcomes among adolescents. This integrated prospective cohort provides an opportunity to characterise long-term HIV treatment outcomes among ALHIV in Africa. We will investigate how individual, familial, community and healthcare experiences in childhood, and adolescence shape these outcomes. Since the COVID-19 pandemic happened during the period of matched data, we will also investigate the potential effect of the COVID-19 pandemic on adolescent HIV treatment outcomes, with potential subgroup analyses for individuals with available COVID-19-related results.

Umbilicated papules in an immunocompromised patient.

A 68-year-old male with HIV (CD4 count: 167 cells/mm³) presented with multiple umbilicated papules on the face and chest and a giant pedunculated nodule on the forehead, persisting for six months. Differential diagnoses included molluscum contagiosum, histoplasmosis, and cryptococcosis for the papules, and giant molluscum contagiosum or squamous cell carcinoma for the nodule. Histopathology revealed epidermal hyperplasia with Henderson Patterson bodies, confirming molluscum contagiosum. Fungal stains, cultures, and antigen tests for cryptococcosis and histoplasmosis were negative. The patient was started on highly active antiretroviral therapy (HAART) for immune reconstitution. This case underscores the importance of histopathology in differentiating molluscum contagiosum from opportunistic infections in immunocompromised patients and highlights HAART as a key therapeutic intervention.

Successful viral suppression in a two-year-old child with human immunodeficiency virus infection treated with bictegravir/emtricitabine/tenofovir alafenamide

Background. Adherence to antiretroviral therapy (ART) is a major challenge in pediatric human immunodeficiency virus (HIV) management, especially in young children due to medication formulation, administration difficulties, and psychosocial barriers. Single-tablet regimens (STRs) have been shown to improve adherence and viral suppression in adults and adolescents, yet their use in younger children remains limited. Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is an STR with a high genetic barrier to resistance, making it a promising option for pediatric patients with adherence difficulties. Case Presentation. We report a case of a 2-year-old girl with perinatally acquired HIV who experienced persistent viremia despite multiple ART regimens. The mother received zidovudine prophylaxis during delivery, and the infant was started on zidovudine (AZT) prophylaxis on the first day of life. The patient’s ART history included AZT monotherapy at birth, followed by combination therapy with lamivudine (3TC), lopinavir/ritonavir (LPV/r), and later tenofovir/emtricitabine (TDF/FTC) with dolutegravir (DTG). Despite these regimens, poor adherence related to medication administration difficulties and caregiver challenges contributed to persistent viremia. A multidisciplinary team approach was implemented to address adherence barriers. Given the patient’s ongoing virological failure and resistance mutations (L76V and V179E), off-label use of BIC/FTC/TAF (50mg/200mg/25mg) was approved. The dosage was adjusted based on weight, and medication administration was closely monitored. Within one month of treatment, HIV RNA levels significantly declined from 1,800,000 to 207 copies/mL. Viral suppression was maintained over subsequent three-month intervals, with HIV RNA levels of 35, 40, and 43 copies/mL, alongside immune recovery as indicated by increased CD4 counts. Conclusion. The successful off-label use of BIC/FTC/TAF in a treatment-refractory pediatric HIV case highlights its potential efficacy in young patients facing adherence challenges. Its high genetic barrier to resistance and favorable tolerability make it a promising option when standard therapies fail. Further research is needed to optimize pediatric ART strategies and expand access to STRs globally.

Meta-analysis of TB & HIV co-infection mortality rate in sub-Saharan African children, youth, and adolescents

BackgroundDespite the effectiveness of antiretroviral treatment (ART) in reducing morbidity and mortality, children and adolescents with co-infections face an elevated risk of death due to their young age and compromised immune systems. While risk factors for tuberculosis (TB) and adverse TB outcomes in HIV-infected adults are well-documented for mortality estimation, understanding mortality risks among HIV-infected children and adolescents, especially in the era of test and treatment and universal ART for all HIV-infected persons, remains limited. This study aimed to estimate the mortality rate among TB and HIV-co-infected children in Sub-Saharan African countries using SRM.MethodsWe systematically searched relevant studies from seven international electronic databases. Articles were searched using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Article searching included six electronic databases including PubMed/MEDLINE (N = 1287), Scopus (N = 447), Web of Science (N = 174), Science Direct (N = 749, Cochran (N = 57), and Google Scholar and research repository bases searching (N = 42). The quality of primary studies was evaluated using Joanna Briggs Institute (JBI) checklist. The pooled mortality rate was estimated using a weighted inverse variance random-effect meta-analysis. Heterogeneity among studies was assessed using Cochran's Q test and estimated using I2 statistic. This document is registered in Prospero (CRD420251012913).ResultIn this SRM, 16 individual studies were included. During the co-infected mortality screening of 5,098 participants, 657 deaths were reported after co-treatment started. The pooled mortality burden was estimated at 12.96% (95% CI: 8.94 to 16.98, I2 = 92.6%, P = 0.001). The majority of TB co-infected cases were newly diagnosed after ART started. The final weighted inverse variance random-effect regression indicated WHO stages III and IV (pooled HR = 4.34), poor/ fair ART adherence (pooled HR = 3.11), missed Isoniazid preventive therapy (IPT) (pooled HR = 3.07), hemoglobin levels ≤ 10 mg/dL (pooled HR = 2.84), bedridden functional status (pooled HR = 3.19), below threshold CD4 count (pooled HR = 1.80), and missed cotrimoxazole preventive therapy (CPT) (pooled AOR = 1.58) were predictors of premature death during co-infection.ConclusionIn this review, the overall pooled burden of mortality in HIV-infected children in SSA countries was high compared with the End TB Strategy target estimation. Significant predictors of mortality included WHO clinical stages III and IV, poor or fair ART adherence, missed Isoniazid preventive therapy (IPT), and hemoglobin levels ≤ 10 mg/dL. Therefore, counseling on antiretroviral therapy adherence should be strengthened; early screening and treating of anemia, screening and scaling up of IPT, critical ART drug, and nutritional counseling should be done during regular visits for caregivers to prevent premature deaths among children, youths, and adolescents during co-infection in SSA.

Retention outcomes during same-day antiretroviral therapy initiation in health facilities and outreach settings of Rakai, Uganda, 2016-2021.

The antiretroviral therapy (ART) initiation policy in Uganda recommends that ART is initiated on the same day of HIV diagnosis to those who do not have contraindications. We assessed determinants of retention in ART care at the first follow-up (FFU) after same-day ART initiation and retention in long-term care beyond the FFU visit. We conducted a retrospective longitudinal analysis among persons living with HIV aged ≥18 years who initiated ART during April 2016-February 2021 after the inception of Uganda's Test-and-Treat ART policy, which states that 'all individuals diagnosed with HIV should initiate ART regardless of clinical stage CD4 count'. Missing the FFU after ART initiation (missing FFU) was defined as not returning for FFU within 1 month of ART initiation; loss to follow-up long-term (LTFU-LT) was defined as delaying more than 3 months to return for a scheduled ART drug refill after the FFU appointment. LTFU-LT time was defined as the time from the FFU visit date to the last follow-up visit date during the study period. We used log-binomial distributions to estimate unadjusted and adjusted relative risks (adjRRs) of missing FFU, and we used Cox proportional hazard models to estimate unadjusted and adjusted hazard ratios (adjHRs) for LTFU-LT. Overall, 8332 clients initiated ART on the same day of HIV diagnosis. Most were female (55%), aged 25-34 years (44%), resided in the semi-urban or rural district (41% and 41%, respectively) and had a median age of 25 years (IQR = 24-35). Overall, missing FFU was 15.1%. Increased likelihood/risk of missing FFU was seen in clients who initiated ART at outreach health service centres versus health facilities (adjRRs = 1.79, 95% CI = 1.6-2.0), in younger clients aged 18-24 years and 25-34 years versus ≥45 years [(adjRRs = 1.65, 95% CI = 1.3-2.0) and (adjRRs = 1.31, 95% CI = 1.1-1.6), respectively], and clients residing in agrarian districts versus fishing districts (adjRRs = 1.24, 95% CI = 1.1-1.4). Overall, the LTFU-LT rate was 25 clients/100 pys (95% CI = 23.9-25.9) and was associated with younger age (18-34 years versus ≥45 years, adjHRs = 1.77, 95% CI = 1.5-2.1), residence in semi-urban (adjHRs = 1.33, 95% CI = 1.2-1.5) or agrarian district (adjHRs = 1.30, 95% CI = 1.2-1.5) versus fishing-community district. Retention-strengthening strategies in tandem with same-day ART initiation efforts for younger clients and clients initiated on ART from mobile and outreach health service settings might improve HIV treatment retention. Best practices for retaining fishing-community clients might improve health outcomes if applied to agrarian and semi-urban communities.

“If your CD4 count lowers, that is when you are similar to a person that is non-existent” A qualitative exploration of perceptions around advanced HIV disease in South Africa

BackgroundDespite widespread availability and differentiated delivery of antiretroviral treatment (ART), advanced HIV disease (AHD) remains prevalent, with high mortality risk. In South Africa, we assessed perceptions about the meaning of AHD and social and behavioural factors influencing AHD development.MethodsIn-depth interviews were conducted with 13 PWH screened for AHD during a community-based tuberculosis triage trial, and five stakeholders involved in policy-making or implementation of AHD-related programmes. Two focus group discussions were conducted with seven study nurses and two with seven public sector nurses. Thematic analysis and data triangulation were performed.ResultsWe found that PWH did not commonly know the term AHD and confused CD4 count with viral load testing. Perceptions about AHD among PWH ranged from AHD being a death sentence, causing opportunistic infections, to AHD diagnosis presenting a survival opportunity. Adherence problems and clinic avoidance were behavioural factors directly leading to AHD, with ART fatigue being emphasized by and in aging PWHs. The main themes which arose when discussing factors influencing AHD development, which were confirmed by different stakeholders, were (i) missed opportunities to (re)-engage in care due to clinic barriers, (ii) emotional stress and impaired mental health, (iii) alternative beliefs about medicines and health, and (iv) stigma, denial, and non-disclosure.ConclusionsThe term “AHD” was commonly unknown among PWH, while opportunistic infections were known. Structural barriers to care, mental health challenges, reliance on traditional medicine, and stigma, contributed to disengagement from care and progression to AHD in our population. These findings highlight the need to raise awareness about AHD among PWH and to create demand for CD4 testing, to implement effective welcome-back strategies for those disengaging from care, integration of mental health screening for PWHs, and revamping community education to reduce stigma and improve ART and AHD-related literacy.Trial registrationClinicaltrials.gov: NCT05526885, 02 September 2022.

Different CMV-specific effector T cell subtypes are associated with age, CMV serostatus, and increased systolic blood pressure

BackgroundCytomegalovirus (CMV) infection is one of the most common infections in humans, and CMV antigens are the major drivers of repetitive T-cell stimulation as a part of a well-adapted immune response in immunocompetent individuals. With higher age, the recurrent clonal expansion of CMV-specific T cells results in high frequencies of CMV-specific effector T cells. Further on, CMV seropositivity has been linked to an increased risk of developing cardiovascular diseases (CVD). Here we investigated the frequency and phenotype of CMV-specific T cells in the circulation of a population cohort of 650 individuals focusing on the age group over 60 years. Circulating immune cells of individuals carrying the HLA-A*02 allele were investigated (n = 302) applying MHC class I tetramers.ResultsWe add to previous knowledge by showing that the frequency of CMVpp65-specific CD8+ T cells is associated with the total percentage and absolute counts of CD8+ and CD4+CD8+ double-positive T cells within leukocytes, and further with systolic blood pressure (SBP) and history of CVD. An investigation into the differentiation status of CMV-specific T cells revealed an association of higher age and increased frequencies of both TEM and CD27-expressing TEMRA cells. In contrast, higher CMV-IgG titers were found to be associated with TEM and CD27− TEMRA cell frequencies. SBP significantly correlated with CMV-specific effector CD8+ T cells, which was mostly reflected by CD27− TEMRA cells.ConclusionsWithin the circulating CMV-specific T cell population, different effector T-cell subtypes were associated with age, serostatus and SBP. This suggests that it is not age or infection per se that render CMV-positive individuals susceptible to CVD, but rather the cellular immune response to CMV. Detailed immunophenotyping may identify individuals whose immune systems are strongly influenced by the response to CMV, leading to health consequences and impairing healthy aging.

CD4+ T cell and CD8+ T Cell Count with their Ratio in Patients of Leprosy Before and After Treatment

Immunological disturbances have often been described in leprosy patients-more so in the lepromatous (LL) than in the tuberculoid (TT) end of the clinicopathological spectrum of the disease. Studies suggested that active lepromatous patients showed a significant lymphopenia and a significant proportionate reduction in the number of OKT3-positive (Pan T), OKT4-positive (Helper/inducer/CD4), and OKT8-positive (Suppressor/cytotoxic/CD8) cells, but no alteration in distribution as judged by percentage and no abnormality in the helper-suppressor ratio. This research work was performed at the department of microbiology and clinical pathology, department of medicine, Sylhet MAG Osmani Medical College and Hospital, Sylhet; and leprosy hospital, Sheikhghat, Sylhet, during the period of January 2012 to December 2012. The objective of the study was to determine cell-mediated immunity by measuring CD4+ and CD8+ cells, and their ratio in patients with leprosy before and after treatment. In this quasi-experimental study, 30 patients with leprosy were enrolled to measure the status of CD4 and CD8 cell counts with their ratios before intervention, and the values were compared to the second sample from the same patients who had multi-drug treatment for leprosy. Lymphocyte count (p&lt;0.001) significantly increased after treatment of leprosy. CD4+ T cell count (p&lt;0.001) and CD8+ T cell count (p=0.001) were significantly increased after treatment of all 30 leprosy cases, with no significant changes in the CD4+/CD8+ ratio (p=0.072). CD4+ T cell count (p=0.001) and CD8+ T cell count (p=0.018) were significantly increased after treatment of the 17 specific lepromatous leprosy cases, and there was no significant change in the CD4+/CD8+ ratio (p=0.070) in the same cases. The immune parameter showed a significantly upward change in the form of a raised lymphocyte count, and CD4+ and CD8+ T cell counts, while CD4+/CD8+ ratios are insignificantly raised after treatment of leprosy and also of lepromatous leprosy. Jalalabad Med J 2023; 20 (2): 54-59

Cost-Utility and Budget Impact Analyses of Herpes Zoster Vaccines in Patients With Human Immunodeficiency Virus in Thailand.

Cost-Utility and Budget Impact Analyses of Herpes Zoster Vaccines in Patients With Human Immunodeficiency Virus in Thailand.

The frequency of CD3+ lymphocytes in non-myocarditis endomyocardial biopsies.

The frequency of CD3+ lymphocytes in non-myocarditis endomyocardial biopsies.

Emerging Infections Network Survey of Screening for Cryptococcal Antigenemia, United States, 2024.

We polled infectious disease specialists about cryptococcal antigen screening for patients initiating HIV antiretroviral therapy. Of 215 respondents, 33% reported typically obtaining screening for patients with CD4 counts <200 cells/mm3 and 63% for counts <100 CD4 cells/mm3. Uncertainty about cryptococcal antigen screening benefits and recommendations suggests opportunities for education and increased screening.

Low-level viremia increases the risk of diabetes mellitus in people with HIV in China: a 7-year retrospective longitudinal cohort study

BackgroundIt is unclear whether low-level viremia (LV) during antiretroviral therapy (ART) increases the incidence of diabetes mellitus (DM). This study aims to assess the association between HIV viremia exposure during ART and DM using retrospective cohort data.MethodsPeople with HIV (PWH) who started ART in 2003 or later were identified from China’s National Free ART Program database. Participants who had been on ART for ≥ 6 months without DM at enrollment were included in this study. Based on two consecutive viral load measurements after 6 months of ART, participants were categorized into three groups: viral suppression (VS), transient episode low-level viremia (blips), and persistent low-level viremia (LLV). Blips and LLV were collectively classified as the LV group. We analyzed the incidence of DM depending on viremia exposure using Cox proportional hazard models adjusted for age, sex, baseline viral load, CD4 count, ART initiation regimen, ART initiation period, and WHO HIV stage. Heterogeneous linear mixed models identified fasting blood glucose (FBG) trajectory patterns during the follow-up.ResultsDuring 26,097 person-years of follow-up, we observed 1297 cases of DM in 8731 participants, with a median follow-up of 2.4 years (IQR: 1.2, 4.5). Two distinct FBG trajectories, labeled “Stable” and “Rapid increase,” were identified. The LLV group had a significantly higher proportion of participants in the “Rapid increase” trajectory (OR: 2.53, p < 0.001). Both the blips (cHR: 1.40, p < 0.001) and LLV (cHR: 1.74, p < 0.001) groups were associated with a higher incidence of DM compared to the VS group. After propensity score matching, the LV group showed a higher DM risk (aHR: 1.27, p = 0.012). When restricted to the 35–49 age group, the risk of DM was even higher in both the LLV (aHR: 2.03, p = 0.017) and blips (aHR: 1.36, p = 0.027) groups compared to the VS group.ConclusionsLow-level viremia (LV) substantially increased the risk of diabetes mellitus (DM) among PWH, particularly in middle-aged individuals. Monitoring viral load and FBG is crucial to prevent DM development and improve life expectancy among ART patients.